Nerandomilast a "No-Brainer" for First-Line Pulmonary Fibrosis Therapy: Justin M. Oldham, MD, PhD, MS

Nerandomilast has demonstrable safety and tolerability, according to pooled late-breaking data presented today at the European Respiratory Society Congress 2025 by FIBRONEER steering committee member Justin M. Oldham, MD, PhD, MS, pulmonary fibrosis specialist, director of interstitial lung disease, and clinical associate professor of internal medicine at the University of Michigan Medical School.

These pooled data cover results from the phase 3 FIBRONEER-IPF (NCT05321069) and FIBRONEER-ILD (NCT05321082) trials over the prolonged exposure time of 76 weeks, or a mean observation time of 16.7 months, and also the final database lock, of patients who received either 9 mg or 18 mg of nerandomilast. The primary end point was vital capacity over 52 weeks.

Among the findings of note, there was a nominally significant association for improved survival, or 59% reduced risk of death, associated with the 18-mg dose of the phosphodiesterase 4B inhibitor.

In this interview, Oldham addresses unmet patient needs that nerandomilast could fulfill should it receive a full approval from the FDA—it has already received breakthrough therapy and orphan drug designations—and his belief in its ability to be a potential front-line agent because of its efficacy, safety, and tolerability profile.

This transcript was lightly edited for clarity; captions were auto-generated.

Transcript

What are the key takeaways from your late-breaking abstract on the pooled data from the FIBRONEER-IPF and FIBRONEER-ILD trials?

The poster I presented today was a pooled analysis of the IPF [idiopathic pulmonary fibrosis] and PPF [progressive pulmonary fibrosis] trials. The populations were all patients included in both trials, and what we did was assess, again, the primary end point through the final database lock, which had more exposure time than the initial database lock of the prior publications, and then we assessed the key secondary end point and the components of the key secondary end point, including respiratory hospitalization, acute exacerbation, and death.

Key findings were that over the prolonged exposure time, so 76 weeks now instead of 52 weeks, we see continued separation in the NPC [normal probability curve] curves when assessing the key secondary end point. This remained a negative finding. But when you dive deeper into the components underpinning the key secondary end point, we see that there is now a nominally significant association for improved survival in those who were treated with nerandomilast 9 or 18 mg.

Can you explain why nerandomilast is so effective against idiopathic and progressive pulmonary fibrosis, and how does it compare with currently approved therapies?

Nerandomilast is a preferential phosphodiesterase 4B inhibitor, which is thought to have both immunomodulatory and antifibrotic effects. Compared to currently approved therapies, what we can say through the FIBRONEER trials is that the addition of nerandomilast to pirfenidone and nintedanib slows FVC [forced vital capacity] decline more than these drugs alone. What we can also say is that in treatment-naïve patients, the drug also slows FVC decline relative to placebo. What we conclude from this is that nerandomilast can likely be used as either a monotherapy or add-on therapy to currently approved drugs.

What insights can you share on nerandomilast's safety and tolerability across doses in FIBRONEER-ILD and -IPF?

The fact that we didn't hit the key secondary end point was disappointing, but I think what was reassuring was when we did a deeper dive into the components of the key secondary end point, death specifically is probably the best hard measure we have in the field, and we did see movement in that number with these doses, especially with the prolonged exposure time.

Did certain patient subgroups appear to derive greater benefit from nerandomilast, and what may have been contributing factors in this variation?

We did see an interesting effect with the treatment-naive patients who were not on background therapy. They seemed to have a larger benefit than those who were treated with background nintedanib or pirfenidone. Whether this is a biologic benefit, I don't think it's entirely clear because it did seem

that those who came into the trial on background therapy were probably sicker and more progressive to start with, and so I don't know that it's a fair comparison to say that those who are not receiving background therapy are systematically the same group of patients as those who are not.

Considering the outcomes related to exacerbations and mortality, how do you see nerandomilast fitting into the current treatment landscape for IPF and PPF?

In a perfect world where payers are not an issue, I see nerandomilast becoming a first-line agent for this disease, and that's both because of the primary efficacy data, but also the tolerability and safety. You know it's a safe drug. There was some diarrhea with it, but hardly anybody stopped the trial because of diarrhea, and it was much less than we see in nintedanib—so, effective [and] safe. There was no LFT [liver function tests] abnormalities, so we're not going to have to follow longitudinal liver function tests in these patients. For me as a clinician, it's a no-brainer that this is first-line therapy.

What are the next steps in the clinical development of nerandomilast based on these current data?

There are trials ongoing using nernadomilast for different key patient groups that are at risk. I think the trial that's needed next is to formally assess the role of nerandomilast as monotherapy vs nerandomilast plus nintedanib or another antifibrotic drug as add-on therapy.

Reference

Oldham JM, Assassi S, Azuma A, et al. Late breaking abstract - safety and tolerability of nerandomilast in patients with pulmonary fibrosis: pooled data from the FIBRONEER-IPF and FIBRONEER-ILD trials. Presented at: ERS Congress 2025; September 27-October 1, 2025; Amsterdam, Netherlands. Poster 2977.